992 resultados para Ferrari, Gaudenzio, approximately 1470-1546.


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Background Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease. Methods and Findings Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders.Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%-10.8%) of global YLDs and dysthymia for 1.4% (0.9%-2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%-3.2%) of global DALYs and dysthymia for 0.5% (0.3%-0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%-3.8%) to 3.8% (3.0%-4.7%) of global DALYs. Conclusions GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden.Please see later in the article for the Editors' Summary.

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Background The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010's mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders. Methods Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty). Results Mental and substance use disorders were responsible for 22.5 million (14.8-29.8 million) of the 36.2 million (26.5-44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%-60.8%)) and anorexia nervosa the lowest (0.2% (0.02%-0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20-30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%-8.6%) to 8.3% (7.1%-9.6%) of global DALYs, and would have changed the global ranking from 5th to 3rd leading cause of burden. Conclusions Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.

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A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.

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Background Summarizing the epidemiology of major depressive disorder (MDD) at a global level is complicated by significant heterogeneity in the data. The aim of this study is to present a global summary of the prevalence and incidence of MDD, accounting for sources of bias, and dealing with heterogeneity. Findings are informing MDD burden quantification in the Global Burden of Disease (GBD) 2010 Study. Method A systematic review of prevalence and incidence of MDD was undertaken. Electronic databases Medline, PsycINFO and EMBASE were searched. Community-representative studies adhering to suitable diagnostic nomenclature were included. A meta-regression was conducted to explore sources of heterogeneity in prevalence and guide the stratification of data in a meta-analysis. Results The literature search identified 116 prevalence and four incidence studies. Prevalence period, sex, year of study, depression subtype, survey instrument, age and region were significant determinants of prevalence, explaining 57.7% of the variability between studies. The global point prevalence of MDD, adjusting for methodological differences, was 4.7% (4.4–5.0%). The pooled annual incidence was 3.0% (2.4–3.8%), clearly at odds with the pooled prevalence estimates and the previously reported average duration of 30 weeks for an episode of MDD. Conclusions Our findings provide a comprehensive and up-to-date profile of the prevalence of MDD globally. Region and study methodology influenced the prevalence of MDD. This needs to be considered in the GBD 2010 study and in investigations into the ecological determinants of MDD. Good-quality estimates from low-/middle-income countries were sparse. More accurate data on incidence are also required.

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Objective. To estimate the burden of disease attributable to excess body weight using the body mass index (BMI), by age and sex, in South Africa in 2000. Design. World Health Organization comparative risk assessment (CRA) methodology was followed. Re-analysis of the 1998 South Africa Demographic and Health Survey data provided mean BMI estimates by age and sex. Populationattributable fractions were calculated and applied to revised burden of disease estimates. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis. Setting. South Africa. Subjects. Adults 30 years of age. Outcome measures. Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, hypertensive disease, osteoarthritis, type 2 diabetes mellitus, and selected cancers. Results. Overall, 87% of type 2 diabetes, 68% of hypertensive disease, 61% of endometrial cancer, 45% of ischaemic stroke, 38% of ischaemic heart disease, 31% of kidney cancer, 24% of osteoarthritis, 17% of colon cancer, and 13% of postmenopausal breast cancer were attributable to a BMI 21 kg/m2. Excess body weight is estimated to have caused 36 504 deaths (95% uncertainty interval 31 018 - 38 637) or 7% (95% uncertainty interval 6.0 - 7.4%) of all deaths in 2000, and 462 338 DALYs (95% uncertainty interval 396 512 - 478 847) or 2.9% of all DALYs (95% uncertainty interval 2.4 - 3.0%). The burden in females was approximately double that in males. Conclusions. This study shows the importance of recognising excess body weight as a major risk to health, particularly among females, highlighting the need to develop, implement and evaluate comprehensive interventions to achieve lasting change in the determinants and impact of excess body weight.

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Over recent years, the health, transport and environment sectors have been increasingly focused on the promotion of transport cycling. From a health perspective, transport cycling is recognised as a beneficial form of physical activity as it can be easily integrated into daily living, is done at an intensity that confers health benefits, and is associated with reductions in mortality and morbidity [1]. From a safety perspective, the risk of a serious cycling injury decreases as cycling increases [2] as having more cyclists on roads increases motor vehicle drivers’ awareness of cyclists and in turn makes cycling safer. Whereas cycling for recreation is the fourth most commonly reported physical activity among Australian adults [3], transport cycling is an underutilised travel mode. Approximately 1.3% of journeys to work in Australia are made by bicycle [4]. This low prevalence is mirrored in the UK and the US, but not in some European countries like the Netherlands and Denmark, where over 18% and 26%, respectively, of all journeys are made by bicycle [5]. In the past decade, concerted efforts have been made by Australian state and local governments to increase cycling rates [6]. Notably, Melbourne, Sydney and Brisbane have implemented policies, increased bicycle commuting infrastructure, and offered information and promotion programs to encourage commuter cycling [6,7]. Governments have also developed comprehensive longterm plans for guiding future cycling strategies, using lessons learned from around the world in developing successful cycling policy and promotion [6,7]. Changes in transport cycling rates in inner cities since these efforts have been implemented are encouraging. In Sydney, census data indicate an 83% increase in the number of people using a bicycle for commuting between 2001 and 2011 [8]. Counts of bicycles being ridden along major cycling commuter routes indicate increases in weekday morning cycling trips in Brisbane (63% increase from 2004 to 2010) [7] and in Melbourne (a 43% increase from 2006 to 2008) [9]. However, bicycle mode share to work has changed little: for example, between 2001 and 2011, it decreased slightly from 1.6% to 1.3% in Brisbane [10,11]. Researchers have been investigating factors that may be contributing to low rates of cycling for transport, to inform future policy and programming to encourage transport cycling. The aim of this paper is to overview our work to date in this area of research in Queensland.

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A modification to the PVA-FX hydrogel whereby the chelating agent, xylenol orange, was partially bonded to the gelling agent, poly-vinyl alcohol, resulted in an 8% reduction in the post irradiation Fe3+ diffusion, adding approximately 1 hour to the useful timespan between irradiation and readout. This xylenol orange functionalised poly-vinyl alcohol hydrogel had an OD dose sensitivity of 0.014 Gy−1 and a diffusion rate of 0.133 mm2 h−1. As this partial bond yields only incremental improvement, it is proposed that more efficient methods of bonding xylenol orange to poly-vinyl alcohol be investigated to further reduce the diffusion in Fricke gels.

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This study examines the effects of temporary tissue expanders (TTEs) on the dose distributions of photon beams in breast cancer radiotherapy treatments. EBT2 radiochromic film and ion chamber measurements were taken to quantify the attenuation and backscatter effects of the inhomogeneity. Results illustrate that the internal magnetic port present in a tissue expander causes a dose reduction of approximately 25% in photon tangent fields immediately downstream of the implant. It was also shown that the silicone elastomer shell of the tissue expander reduced the dose to the target volume by as much as 8%. This work demonstrates the importance for an accurately modelled high-density implant in the treatment planning system for post-mastectomy breast cancer patients.

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Electrical resistivity of soils and sediments is strongly influenced by the presence of interstitial water. Taking advantage of this dependency, electrical-resistivity imaging (ERI) can be effectively utilized to estimate subsurface soil-moisture distributions. The ability to obtain spatially extensive data combined with time-lapse measurements provides further opportunities to understand links between land use and climate processes. In natural settings, spatial and temporal changes in temperature and porewater salinity influence the relationship between soil moisture and electrical resistivity. Apart from environmental factors, technical, theoretical, and methodological ambiguities may also interfere with accurate estimation of soil moisture from ERI data. We have examined several of these complicating factors using data from a two-year study at a forest-grassland ecotone, a boundary between neighboring but different plant communities.At this site, temperature variability accounts for approximately 20-45 of resistivity changes from cold winter to warm summer months. Temporal changes in groundwater conductivity (mean=650 S/cm =57.7) and a roughly 100-S/cm spatial difference between the forest and grassland had only a minor influence on the moisture estimates. Significant seasonal fluctuations in temperature and precipitation had negligible influence on the basic measurement errors in data sets. Extracting accurate temporal changes from ERI can be hindered by nonuniqueness of the inversion process and uncertainties related to time-lapse inversion schemes. The accuracy of soil moisture obtained from ERI depends on all of these factors, in addition to empirical parameters that define the petrophysical soil-moisture/resistivity relationship. Many of the complicating factors and modifying variables to accurately quantify soil moisture changes with ERI can be accounted for using field and theoretical principles.

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The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

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Background The frequency of prescribing potentially inappropriate medications (PIMs) in older patients remains high regardless of the evidence of adverse outcomes from their use. This study aims to identify the prevalence and nature of PIMs at admission to acute care and at discharge to residential aged care facilities (RACFs) using the recently updated Beers’ Criteria. We also aim to identify if polypharmacy, age, gender and the frailty status of patients are independent risk factors for receiving a PIM. Methods This was a retrospective study of 206 patients discharged to RACFs from acute care. All patients were aged at least70 years and were admitted between July 2005 and May 2010; their admission and discharge medications were evaluated. Frailty status was measured as the Frailty Index (FI), adding each individual’s deficits and dividing by the total number of deficits considered, with FI 0.25 used as the cut-off between “fit” and “frail”. Results Mean patient age was 84.8 ± 6.7 years; the majority (57%) were older than 85 years and approximately 90% were frail. Patients were prescribed a mean of 7.2 regular medications at admission and 8.1 on discharge. At least one PIM was identified in 112 (54.4%) patients on admission and 102 (49.5%) patients on discharge. Of all medications prescribed at admission (1728), 10.8% were PIMs and at discharge of 1759 medications, 9.6% were PIMs. Of the total 187 PIMs on admission, 56 (30%) were stopped, and 131 were continued; 32 new PIMs were introduced. Commonly prescribed PIMs at both admission and discharge were central nervous system, cardiovascular and gastrointestinal drugs and analgesics. Of the potential risk factors, frailty status was the only significant predictor of PIMs at both admission and discharge (p = 0.016). Conclusion A high prevalence of unnecessary drug use was observed in frail older patients on admission to acute care hospitals and on discharge to RACFs. The only association with PIM use was the frailty status of patients. Further studies are needed to further evaluate this association.

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This paper presents the most recent data on cancer rates and the burden of cancer in the ASEAN region. Epidemiological data were sourced from GLOBOCAN 2008 and disability adjusted life years (DALYs) lost were estimated using the standard methodology developed within the World Health Organization's Global Burden of Disease study. Overall, it was estimated there were over 700,000 new cases of cancer and 500,000 cancer deaths in ASEAN in the year 2008, leading to approximately 7.5 million DALYs lost in one year. The most commonly diagnosed cancers were lung (98,143), breast (86,842) and liver cancers (74,777). The most common causes of cancer death were lung cancer (85,772), liver cancer (69,115) and colorectal cancer (44,280). The burden of cancer in terms of DALYs lost was highest in Laos, Viet Nam and Myanmar and lowest in Brunei, Singapore and the Philippines. Significant differences in the patterns of cancer from country to country were observed. Another key finding was the major impact played by population age distribution on cancer incidence and mortality. Cancer rates in ASEAN are expected to increase with ageing of populations and changes in lifestyles associated with economic development. Therefore, ASEAN member countries are strongly encouraged to put in place cancer-control health carepolicies, focussed on strengthening the health systems to cope with projected increases in cancer prevention, treatment and management needs.

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BACKGROUND Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

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Background We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). Methods For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980–2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. Findings In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million–216·7 million), or 7·4% (6·2–8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million–12·1 million; 0·5% [0·4–0·7] of all YLLs) and 175·3 million YLDs (144·5 million–207·8 million; 22·9% [18·6–27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7–49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2–18·4), illicit drug use disorders for 10·9% (8·9–13·2), alcohol use disorders for 9·6% (7·7–11·8), schizophrenia for 7·4% (5·0–9·8), bipolar disorder for 7·0% (4·4–10·3), pervasive developmental disorders for 4·2% (3·2–5·3), childhood behavioural disorders for 3·4% (2·2–4·7), and eating disorders for 1·2% (0·9–1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10–29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. Interpretation Despite the apparently small contribution of YLLs—with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm—our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority.

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A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A new methodology for the derivation of atomic hydrophobicity from any amino acid-based hydrophobicity scale was used to derive 8 sets of atomic hydrophobicities, one of which was used to generate the molecular surfaces for 35 proteins with convex structures, 5 of which, i.e., lysozyme, ribonuclease, hemoglobin, albumin and IgG, have been analyzed in more detail. Sets of the molecular surfaces of the model proteins have been constructed using spherical probes with increasingly large radii, from 1.4 to 20 A˚, followed by the quantification of (i) the surface hydrophobicity; (ii) their respective molecular surface areas, i.e., total, hydrophilic and hydrophobic area; and (iii) their relative densities, i.e., divided by the total molecular area; or specific densities, i.e., divided by property-specific area. Compared with the amino acid-based formalism, the atom-level description reveals molecular surfaces which (i) present an approximately two times more hydrophilic areas; with (ii) less extended, but between 2 to 5 times more intense hydrophilic patches; and (iii) 3 to 20 times more extended hydrophobic areas. The hydrophobic areas are also approximately 2 times more hydrophobicity-intense. This, more pronounced "leopard skin"-like, design of the protein molecular surface has been confirmed by comparing the results for a restricted set of homologous proteins, i.e., hemoglobins diverging by only one residue (Trp37). These results suggest that the representation of hydrophobicity on the protein molecular surfaces at atom-level resolution, coupled with the probing of the molecular surface at different geometric resolutions, can capture processes that are otherwise obscured to the amino acid-based formalism.